CD4⁺ T cells can differentiate into numerous subsets characterized by expression of a suite of cytokines and effector molecules that endow them with specialized functions. By mediating the differentiation of B cells into memory and plasma cells following exposure to T-dependent antigens (Ag), T follicular helper (T_FH) cells have emerged as the predominant subset of CD4⁺ T cells responsible for regulating humoral immunity. The generation of T_FH cells from naïve precursors typically involves sequential cognate interactions with distinct populations of Ag-presenting cells (APCs): dendritic cells within the T-cell zone of lymphoid tissues, and activated B cells at the border of the T-zone and follicle, and then within a germinal center. Recent studies have illuminated the key roles of APCs in T_FH development, and have also re-defined the role of B cells in this process.